This proposal presents 11 research projects on syntheses of natural products with established medicinal use, with emphasis on anticancer activity in 7 projects. There are four syntheses of the vindoline system which is the key half of antileukemic vincaleucoblastine. One of these utilizes a new biomimetic oxidative alkylation of indoles, which will also allow conversion of vincamine and its synthetic precursors and analogs to the vindoline system as well as simple syntheses of strychnos and picraline alkaloids, presented as other projects. Nucleophilic addition to pyridinium compounds provides a general pyridine substitution route which will be applied to syntheses of analgetic and antitussive mitragynine and the antihypertensive and tranquilizing drug reserpine as well as to precursors for the preceding drug syntheses. A new route to the iboga alkaloids through oxindole intermediates will provide a first practical synthesis of this alkaloid class which includes antitumor, CNS stimulating, hypotensive, diuretic and hypoglycemic compounds. A novel synthesis of cephalotaxine, the parent alcohol of the anticancer harringtonine esters, is particularly designed to allow structure-activity studies. A new synthetic method will be explored for stereospecific multicenter syntheses of acyclic and macrocyclic compounds, particularly the ansamycin antibiotics rifamycin and streptovaricin. These compounds have antibacterial and antiviral use and show pronounced activity against leukemia and mammary tumors.